With advances in the care and invasive management of critically ill children, venous thromboembolism has become increasingly recognized in pediatrics over the past decade. Optimal treatment of thrombosis in children requires a skilled assessment of acute and long-term prothrombotic tendencies, risk of adverse post-thrombotic outpomes, and potential hemorrhagic complications. To date, the number of pediatric subspecialists who have gained expertise through formal mentored training in both the field of thrombosis/ thrombophilia and the discipline of clinical investigation is limited, and many of these individuals are senior in their careers. At the same time, few randomized controlled trials (RCTs) have provided clinical evidence for the management of thrombosis in children, and guidelines remain largely based upon adult data. Given these critical public health needs, the PRINCIPAL OBJECTIVE of this proposal is to provide the applicant with exceptional mentored training in pediatric thrombosis/thrombophilia and clinical/translational research, and to foster his mentored role in conducting a pilot/feasibility study for an original, web-based RCT (supported by, and performed via the network of, the Hemophilia and Thrombosis Research Society) that seeks to optimize the duration of anticoagulant therapy for venous thrombosis in children. The PRIMARY HYPOTHESIS of the study is that a shortened duration of anticoagulation is as effective, and at least as safe, as conventional-duration anticoagulation in children with acute venous thrombosis in whom early thrombus resolution has occurred and clinical and laboratory features constitute a low-risk for adverse post- thrombotic outcomes. Enrolled children will be treated acutely with anticoagulation according to the present standard of care; patients who demonstrate thrombus resolution radiologically at 6 weeks will then be randomized to undergo no further anticoagulation versus to complete a conventional 3-month course of therapy. Patients will be followed for 2 years with uniform assessment of bleeding complications, recurrent thromboembolism, and the post-thrombotic syndrome, for preliminary safety and efficacy comparison between the two regimens. Enrollment of 200 patients across 10 pilot sites will provide sufficient pilot data for, and demonstrate the feasibility of, the future definitive RCT. Additionally, translational studies will seek to identify novel candidate protein risk factors and prognostic markers for venous thrombosis in children. [unreadable] [unreadable] [unreadable]